The Norwalk and Norwalk-like human caliciviruses are important etiologic agents of epidemic nonbacterial gastroenteritis. A major research obstacle in the study of these viruses has been the inability to grow them in cell culture. A major goal of this project is to develop systems for the study of the basic molecular biology and replication of these fastidious human pathogens. The structural and biological characteristics of the single major structural protein, the capsid, were investigated this year following expression in mammalian cells that are nonpermissive for the growth of Norwalk virus. An advance this year was the construction of a full-length cDNA clone of the Norwalk virus genome. In concert with strategies developed to study the cultivatable feline calicivirus in nonpermissive cells (Project Z01 AI 00707-02 LID), efforts are in progress to "recover" infectious Norwalk virus in a cell culture system employing cDNA clones.